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Clinical therapeutics 1 > Crystals > Flashcards

Crystals Flashcards

1
Q

We assume pharmaceuticals in the solid state are —

A

crystalline

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2
Q

The journey a tablet makes through your body

A
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3
Q

What does it mean when we say crystalline materials have a ‘long range order’

A
  • They are arranged in a regular manner in 3D over huge ranges (thousands of molecules in each direction)
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4
Q

What is the non-crystalline state (amorphous)

A
  • Lack of ‘long range order’
  • Molecules are arranged randomly
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5
Q

How do we describe the structure of a crystal

A
  • Molecular crystals consist of regularly arranged molecules in three dimensions extending
    (effectively) to infinity
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6
Q

What three key pieces of info do we need to know about a crystal

A
  • Size of the unit cell
  • Shape of the unit cell
  • Positions of the atoms in the unit cell
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7
Q

How do we in lab see whether something is crystalline or amorphouse

A
  • Expose it to xrays and look for scattered radiation
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8
Q

What are polymorphs

A
  • Polymorphs can exist in more than one crystalline form
  • Typically two polymorphs of a molecule will differ in: size and shape of unit cells, location of the molecule in the unit cell
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9
Q

What forces hold a solid together?

A
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10
Q

How do polymorphs impact drug properties

A

Polymorphs of the same compound can have different physical and chemical properties, such as:
- Solubility: Some polymorphs may dissolve more readily in bodily fluids, impacting drug absorption and bioavailability.
- Stability: Certain forms might be more stable, while others could degrade faster under specific conditions.
- Melting Point: Different polymorphs may have varying melting points, affecting manufacturing processes.
- Density and Hardness: These can influence tablet compression and drug formulation.

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11
Q

Why might the physicals forms of these polymorphs vary

A
  • Some have week VdW forces, others have this and OH bonds
  • Increase intermolecular interactions, increase thermodynamic favourability, increase tendancy of molecules to leave solid state
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12
Q

the a polymorph has the
higher solubility. How do we explain this observation?
Cs = solubility

A

chat gpt

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13
Q

Forming crystals from a solution (crystallisation) - describe the process five steps

A
  1. Dissolved solid in solvent until a saturated solution is achieved
  2. Remove excess solid from saturated solution
  3. Allow solution to cool or evaporate
  4. Supersaturated solution achieved
  5. Nucleation and crystal growth
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14
Q

polymorphic form can influence —-
of drugs

A

polymorphic form can influence bioavailability
of drugs

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15
Q

Solubility is an important indicator of polymorph stability
Given a particular API, the most stable polymorph will
have the — solubility

A

Solubility is an important indicator of polymorph stability
Given a particular API, the most stable polymorph will
have the lowest solubility

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16
Q

Do polymorphs have good thermodynamic stability?

A
  • They have good solubility BUT
  • Not good thermodynamic stability
  • They tend to revert to (lower solubility) crystalline forms.
  • Hence they arent widely used
17
Q

What are solvates

A
  • Solvates are crystal structures where a solvent is incorprated into the crystal
  • It is not adsorbed or absorbed
  • The solvent is usually incorporated during
    crystallisation, but can sometimes be incorporated
    by exposing a crystal to solvent
18
Q

What are hydrates

A
  • Hydrates are solvates where the solvent in
    question is water
  • Water can also be incorporated from the
    atmosphere e.g. an anhydrous sample is prepared
    and found to gain weight on storage at high relative
    humidity. There is fair chance that water is being
    incorporated into the crystal structure (i.e. a phase
    transformation is taking place) to generate a new
    crystal structure that includes water
  • Once incorporated, it can often be removed by
    heating, inducing a phase transition back to an
    anhydrous form in the process
19
Q

What are co-crystals

A
  • Solid form constituting two or more (neutral) compounds
  • Not a solvate or salt
  • One of the compounds would be the API
20
Q

The solubility of the
(thermodynamically) stable
form of an API is too low to
be used in formulation
Name THREE possible
strategies to improve the
solubility of a poorly soluble API

A

Clinical therapeutics 1 (34 decks)

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